Association of Organochlorine Pesticides With Genetic Markers of Endoplasmic Reticulum Stress in Type 2 Diabetes Mellitus: A Case-Control Study Among the North-Indian Population

Front Endocrinol (Lausanne). 2022 Mar 16:13:841463. doi: 10.3389/fendo.2022.841463. eCollection 2022.

Abstract

Background: Organochlorine pesticides (OCPs) have been long linked to type 2 diabetes mellitus (T2DM); however, this relation at the molecular level has not been explored yet. Endoplasmic reticulum (ER) stress and pro-inflammatory pathways are considered vital ones in the pathogenesis of T2DM. We aimed to investigate the existence of any association between OCPs, ER stress, and pro-inflammatory pathways in subjects with known T2DM.

Methods: Seventy subjects each with T2DM and normal glucose tolerance were recruited from the surgery department. Their visceral adipose tissue was collected intraoperatively. OCP concentration, ER stress, and pro-inflammatory markers were analyzed and compared between two study groups.

Results: We found 18 OCPs and their metabolites in visceral adipose tissue samples of study participants. The levels of δ-HCH, heptachlor, endrin, and p,p'DDT were significantly higher in the T2DM group and were also positively correlated with fasting and postprandial plasma glucose levels (p < 0.01). We observed a positive association of δ-HCH (p < 0.01), heptachlor (p < 0.05), and endrin (p < 0.05) with central adiposity and ER stress markers. However, we failed to establish the correlation of OCPs with any of the pro-inflammatory markers.

Conclusion: The existence and simultaneous complex correlation of OCPs with ER stress may explain their role in the pathogenesis of T2DM, revealing the persistence of the gene-environment interaction in the etiology of T2DM.

Keywords: ER stress; OCP; T2DM; inflammation; normal glucose tolerance; visceral adipose tissue.

MeSH terms

  • Case-Control Studies
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / metabolism
  • Endoplasmic Reticulum Stress
  • Genetic Markers
  • Humans
  • Pesticides*

Substances

  • Genetic Markers
  • Pesticides